State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China.
Nanotechnology. 2010 Mar 26;21(12):125105. doi: 10.1088/0957-4484/21/12/125105. Epub 2010 Mar 5.
As titanium dioxide nanoparticles (TiO(2) NPs) are widely used commercially, their potential toxicity on human health has attracted particular attention. In the present study, the oral toxicological effects of TiO(2) NPs (dosed at 0.16, 0.4 and 1 g kg( - 1), respectively) were investigated using conventional approaches and metabonomic analysis in Wistar rats. Serum chemistry, hematology and histopathology examinations were performed. The urine and serum were investigated by (1)H nuclear magnetic resonance (NMR) using principal components and partial least squares discriminant analysis. The metabolic signature of urinalysis in TiO(2) NP-treated rats showed increases in the levels of taurine, citrate, hippurate, histidine, trimethylamine-N-oxide (TMAO), citrulline, alpha-ketoglutarate, phenylacetylglycine (PAG) and acetate; moreover, decreases in the levels of lactate, betaine, methionine, threonine, pyruvate, 3-D-hydroxybutyrate (3-D-HB), choline and leucine were observed. The metabonomics analysis of serum showed increases in TMAO, choline, creatine, phosphocholine and 3-D-HB as well as decreases in glutamine, pyruvate, glutamate, acetoacetate, glutathione and methionine after TiO(2) NP treatment. Aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) were elevated and mitochondrial swelling in heart tissue was observed in TiO(2) NP-treated rats. These findings indicate that disturbances in energy and amino acid metabolism and the gut microflora environment may be attributable to the slight injury to the liver and heart caused by TiO(2) NPs. Moreover, the NMR-based metabolomic approach is a reliable and sensitive method to study the biochemical effects of nanomaterials.
由于二氧化钛纳米粒子（TiO(2) NPs）在商业上得到广泛应用，其对人类健康的潜在毒性引起了特别关注。在本研究中，采用常规方法和代谢组学分析，研究了 TiO(2) NPs（剂量分别为 0.16、0.4 和 1 g/kg）对 Wistar 大鼠的口服毒性作用。进行了血清化学、血液学和组织病理学检查。采用（1）H 核磁共振（NMR）技术，通过主成分和偏最小二乘判别分析对尿液和血清进行了分析。TiO(2) NP 处理大鼠尿液分析的代谢特征显示，牛磺酸、柠檬酸、马尿酸、组氨酸、三甲胺-N-氧化物（TMAO）、瓜氨酸、α-酮戊二酸、苯乙酰甘氨酸（PAG）和乙酸盐水平升高；而乳酸盐、甜菜碱、蛋氨酸、苏氨酸、丙酮酸盐、3-D-羟基丁酸（3-D-HB）、胆碱和亮氨酸水平降低。血清代谢组学分析显示，TMAO、胆碱、肌酸、磷酸胆碱和 3-D-HB 增加，谷氨酰胺、丙酮酸盐、谷氨酸、乙酰乙酸盐、谷胱甘肽和蛋氨酸减少。TiO(2) NP 处理大鼠的天门冬氨酸氨基转移酶（AST）、肌酸激酶（CK）和乳酸脱氢酶（LDH）升高，心脏组织中线粒体肿胀。这些发现表明，能量和氨基酸代谢以及肠道微生物区系环境的紊乱可能是由于 TiO(2) NPs 对肝脏和心脏造成的轻微损伤所致。此外，基于 NMR 的代谢组学方法是研究纳米材料生化效应的可靠和敏感方法。
